Genetic Variant EMP2:c.*98G>T (chr16-10532807-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001424.6(EMP2):c.*98G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 22)

Exomes 𝑓: 0.00014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EMP2
NM_001424.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0280

Publications

2 publications found

Variant links:

Genes affected

EMP2 (HGNC:3334): (epithelial membrane protein 2) This gene encodes a tetraspan protein of the PMP22/EMP family. The encoded protein regulates cell membrane composition. It has been associated with various functions including endocytosis, cell signaling, cell proliferation, cell migration, cell adhesion, cell death, cholesterol homeostasis, urinary albumin excretion, and embryo implantation. It is known to negatively regulate caveolin-1, a scaffolding protein which is the main component of the caveolae plasma membrane invaginations found in most cell types. Through activation of PTK2 it positively regulates vascular endothelial growth factor A. It also modulates the function of specific integrin isomers in the plasma membrane. Up-regulation of this gene has been linked to cancer progression in multiple different tissues. Mutations in this gene have been associated with nephrotic syndrome type 10 (NPHS10). [provided by RefSeq, Mar 2015]

EMP2 Gene-Disease associations (from GenCC):

nephrotic syndrome, type 10
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

EMP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.19).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001424.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMP2	NM_001424.6	MANE Select	c.*98G>T		3_prime_UTR	Exon 5 of 5	NP_001415.1	P54851

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EMP2	ENST00000359543.8	TSL:1 MANE Select	c.*98G>T	3_prime_UTR	Exon 5 of 5	ENSP00000352540.3	P54851
EMP2	ENST00000867006.1		c.*98G>T	3_prime_UTR	Exon 5 of 5	ENSP00000537065.1
EMP2	ENST00000867008.1		c.*98G>T	3_prime_UTR	Exon 6 of 6	ENSP00000537067.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

101936

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000137

AC:

AN:

101960

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

54846

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000285

AC:

AN:

3506

American (AMR)

AF:

0.00

AC:

AN:

6656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1784

East Asian (EAS)

AF:

0.00

AC:

AN:

5230

South Asian (SAS)

AF:

0.000241

AC:

AN:

8300

European-Finnish (FIN)

AF:

0.000142

AC:

AN:

7036

Middle Eastern (MID)

AF:

0.00

AC:

AN:

320

European-Non Finnish (NFE)

AF:

0.000154

AC:

AN:

64794

Other (OTH)

AF:

0.00

AC:

AN:

4334

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.264

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

101980

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

45898

African (AFR)

AF:

0.00

AC:

AN:

26794

American (AMR)

AF:

0.00

AC:

AN:

6316

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3044

East Asian (EAS)

AF:

0.00

AC:

AN:

2980

South Asian (SAS)

AF:

0.00

AC:

AN:

3082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

124

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

55200

Other (OTH)

AF:

0.00

AC:

AN:

1348

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.19

CADD

Benign

5.6

(source)

DANN

Benign

0.77

PhyloP100

-0.028

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over